Investigations of inherited retinal degeneration of C3H mice and RCS rats are continuing. We are currently interested in the study of cyclic nucleotide metabolism in these retinas. Our observations indicate that cyclic GMP is the predominant cyclic nucleotide of the photoreceptor cells and that cyclic AMP is concentrated in the inner layers of the rodent retina. In the inherited retinal degeneration, both of C3H mice and RCS rats, an abnormality in cyclic GMP metabolism of the photoreceptor cells is detectable a few days before the photoreceptor cells degenerate. In the C3H retina, an abnormality in cyclic GMP metabolism results from a deficiency in cyclic GMP phosphodiesterase activity of the photoreceptor cells. In the RCS retina, an abnormality in cyclic GMP metabolism of the photoreceptor cells is induced by the debris which accumulated in this disorder. Our current work is directed to extending and clarifying the biochemistry of these inherited diseases. An organ culture of the developing mouse eye will be established in which we can study, in a controlled environment, the relationship between cyclic GMP metabolism and photoreceptor cell development or function. The debris which forms in the RCS retina will be analyzed chemically and tested for its interaction with the enzymes of cyclic GMP metabolism. Our work is directed to the goal of identifying the biochemical events which cause photoreceptor degeneration in these diseases. BIBLIOGRAPHIC REFERENCES: Lolley, R.N. and Farber, D.B.: cyclic nucleotide phosphodiesterases in dystrophic rat retinas: Guanosine 3', 5' cyclic monophosphate anomalies during photoreceptor cell degeneration. Exp. Eye Res. 20:585, 1975. Lolley, R.N. and Farber, D.B.: Abnormal guanosine 3', 5' monophosphate during photoreceptor degeneration in the inherited retinal disorder of C3H/H3J mice. Ann. Ophthalmol., 1975.